The role of the different Kunitz domains of TFPI in the down-regulation of the extrinsic coagulation pathway

Haemophilia is a blood clotting disorder that delays clot formation and can be fatal in patients undergoing operations, accidents or injuries. It is caused by low levels of coagulation protein. Present treatment for haemophilia is to reconstitute patients with missing protein but it is an expensive treatment with a risk of developing side effects. Alternative approach is to inhibit the anticoagulants, the regulatory proteins who inhibit coagulant proteins when they are produced in excess. This thesis focuses on how to inhibit TFPI, one of the most important anticoagulant proteins. The mechanism of inhibition of coagulation proteins was studied at domain (small part of protein) level. This study contributes to the biotech or pharma companies to develop inhibitors that can help haemophilic patients to live longer with cheap medication and no side effects.